Brain stimulation: a therapeutic approach for the treatment of neurological disorders

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non-invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well-controlled and effective brain stimulation. Currently, most used non-invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non-invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.     

Transcranial magnetic stimulation in the treatment of psychiatric disorders

Transcranial magnetic stimulation (TMS) is a new technology that applies the principles of electromagnetism to deliver an electrical field to the cerebral cortices. Well established in diagnostic electrophysiology, TMS is now being studied as a treatment for psychiatric disorders. Evidence suggests this technique is safe and acceptable to patients. The future may see the application of TMS in obsessive-compulsive disorder, post-traumatic stress disorder and mania. There is strong evidence that it will become an accepted treatment of depression.     

Challenges of proper placebo control for non‐invasive brain stimulation in clinical and experimental applications

A range of techniques are now available for modulating the activity of the brain in healthy people and people with neurological conditions. These techniques, including transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS, which includes direct and alternating current), create magnetic or electrical fields that cross the intact skull and affect neural processing in brain areas near to the scalp location where the stimulation is delivered. TMS and tCS have proved to be valuable tools in behavioural neuroscience laboratories, where causal involvement of specific brain areas in specific tasks can be shown. In clinical neuroscience, the techniques offer the promise of correcting abnormal activity, such as when a stroke leaves a brain area underactive. As the use of brain stimulation becomes more commonplace in laboratories and clinics, we discuss the safety and ethical issues inherent in using the techniques with human participants, and we suggest how to balance scientific integrity with the safety of the participant.     

The use of noninvasive brain stimulation techniques to improve reading difficulties in dyslexia: A systematic review

Noninvasive brain stimulation (NIBS) allows to actively and noninvasively modulate brain function. Aside from inhibiting specific processes, NIBS may also enhance cognitive functions, which might be used for the prevention and intervention of learning disabilities such as dyslexia. However, despite the growing interest in modulating learning abilities, a comprehensive, up‐to‐date review synthesizing NIBS studies with dyslexics is missing. Here, we fill this gap and elucidate the potential of NIBS as treatment option in dyslexia. The findings of the 15 included studies suggest that repeated sessions of reading training combined with different NIBS protocols may induce long‐lasting improvements of reading performance in child and adult dyslexics, opening promising avenues for future research. In particular, the “classical” reading areas seem to be most successfully modulated through NIBS, and facilitatory protocols can improve various reading‐related subprocesses. Moreover, we emphasize the need to further explore the potential to modulate auditory cortex function as a preintervention and intervention approach for affected children, for example, to avoid the development of auditory and phonological difficulties at the core of dyslexia. Finally, we outline how future studies may increase our understanding of the neurobiological basis of NIBS‐induced improvements in dyslexia.     

Transcranial direct current stimulation in psychiatric disorders

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.     

Transcranial direct current stimulation for the treatment of focal hand dystonia

The treatment of writer's cramp, a task‐specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double‐blind, sham‐controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2‐week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. © 2011 Movement Disorder Society     

Non-invasive electrical brain stimulation: from acute to late-stage treatment of central nervous system damage

Non-invasive brain current stimulation(NIBS) is a promising and versatile tool for inducing neuroplasticity,protection and functional rehabilitation of damaged neuronal systems.It is technically simple,requires no surgery,and has significant beneficial effects.However,there are various technical approaches for NIBS which influence neuronal networks in significantly different ways.Transcranial direct current stimulation(t DCS),alternating current stimulation(ACS) and repetitive transcranial magnetic stimulation(r TMS) all have been applied to modulate brain activity in animal experiments under normal and pathological conditions.Also clinical trials have shown that t DCS,r TMS and ACS induce significant behavioural effects and can – depending on the parameters chosen – enhance or decrease brain excitability and influence performance and learning as well as rehabilitation and protective mechanisms.The diverse phaenomena and partially opposing effects of NIBS are not yet fully understood and mechanisms of action need to be explored further in order to select appropriate parameters for a given task,such as current type and strength,timing,distribution of current densities and electrode position.In this review,we will discuss the various parameters which need to be considered when designing a NIBS protocol and will put them into context with the envisaged applications in experimental neurobiology and medicine such as vision restoration,motor rehabilitation and cognitive enhancement.     

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P  = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS.     

New perspectives on techniques for the clinical psychiatrist: Brain stimulation,chronobiology and psychiatric brain imaging

This review summarizes a scientific dialogue between representatives in non‐pharmacological treatment options of affective disorders. Among the recently introduced somatic treatments for depression those with most evidenced efficacy will be discussed. The first part of this article presents current opinions about the clinical applications of transcranial magnetic stimulation in the treatment of depression. The second part explains the most relevant uses of chronobiology in mood disorders, while the last part deals with the main perspectives on brain imaging techniques in psychiatry. The aim was to bridge gaps between the research evidence and clinical decisions, and reach an agreement on several key points of chronobiological and brain stimulation techniques, as well as on relevant objectives for future research.     

Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging

Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to alter brain activity noninvasively, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional magnetic resonance imaging, positron emission tomography and electroencephalography, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner.     

Repetitive transcranial magnetic stimulation in treatment of post polio syndrome

Background

Post polio syndrome is a rare disease that occurs decades after polio virus infection. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness in drug resistant depression. Possibly it can be helpful in therapy of other neurological diseases including post polio syndrome.

低频rTMS对TBI患者兴奋性毒性指数的影响

目的探讨低频重复经颅磁刺激（rTMS）对颅脑损伤（TBI）患者兴奋性毒性指数（EI）的影响。方法 48例急性TBI患者按GCS评分分为轻型组（MI组）、中型组（MO组）及重型组（SE组）,根据治疗方法每组又分为两亚组,即常规治疗组（c组）及低频rTMS治疗组（r组）,每亚组8例患者。治疗7 d后,采用高效液相色谱法测定患者脑脊液中谷氨酸（Glu）、甘氨酸（Gly）、γ-氨基丁酸（GABA）的浓度并计算出兴奋性毒性指数（EI）=[Glu]×[Gly]/[GABA]。结果对于轻型颅脑损伤患者,与c组相比,r组脑脊液Glu、Gly、GABA浓度及EI均有下降趋势,但无统计学差异（P〉0.05）。对于中型颅脑损伤患者,与c组相比,r组脑脊液Glu、GABA及EI均明显降低（P〈0.05）。对于重型颅脑损伤患者,与c组相比,r组脑脊液Glu、Gly、GABA及EI均明显降低（P〈0.05）。结论低频rTMS可以减轻中、重型TBI患者的兴奋毒性,从而起到脑保护作用。     

Noninvasive brain stimulation combined with other therapies improves gait speed after stroke: a systematic review and meta-analysis

Background: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive brain stimulation (NIBS) techniques able to modulate cortical excitability.

Objective: To determine the effects of NIBS combined with other therapies on gait speed after stroke.

Methods: Electronic databases searched were PUBMED, EMBASE, COCHRANE, SCOPUS, SCIELO and PEDro. Eligibility criteria were randomized controlled trials that reported the effects of tDCS and rTMS combined with other therapies for improving gait speed, walking cadence, functional ambulation category (FAC) and motricity index (MI-LE) after stroke. Risk of bias was assessed by Cochrane risk of bias assessment tool. Mean differences (MD) and 95% confidence intervals were calculated. Quality of evidence was assessed by Grades of Researches, Assessment, Development and Evaluation approach.

Results: Ten studies (226 subjects) were included in the meta-analysis. NIBS combined with other therapies was effective for improving gait speed (MD 0.09 m/s [95% CI, 0.05 to 0.13; I² 0%, p < 0.0001]). Gait speed improved in both acute/subacute (MD 0.08 m/s [95% CI, 0.02 to 0.14]) and chronic phases (MD 0.08 m/s [95% CI, 0.03 to 0.13]). Furthermore, inhibitory (MD 0.09 m/s [95% CI, 0.04 to 0.14]) and excitatory (MD 0.07 m/s [95% CI, 0.02 to 0.12]) protocols were effective to improve gait speed. NIBS was also effective to improve walking cadence but was unable to modify other outcomes (FAC and MI-LE).

Conclusions: This systematic review with meta-analysis synthesizes moderate-quality evidence that NIBS combined with other therapies are effective to improve gait speed after stroke.

Systematic Review registration number: PROSPERO registration number CDR42015024237.